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bioRxiv · 10.64898/2026.11.12.766152

State-dependent structure-function coupling reflects dynamic engagement of the brain's structural scaffold

Pedersen, R.·Sala-Llonch, R.·Persson, J.·Salami, A.
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Abstract

Functional brain organization is shaped by the brain's anatomical scaffold, yet how structure-function coupling varies across cognitive states remains unclear. Across 723 adults from two independent cohorts, we examined coupling using diffusion and functional magnetic resonance imaging. In the primary cohort, coupling was strongest during movie-watching, intermediate during rest, and weakest during working memory, declining further with increasing working-memory load. The movie-rest difference replicated in an independent sample, challenging the primacy of rest for revealing anatomical constraints. State effects were superimposed on a stable unimodal-to-transmodal cortical hierarchy, with movie-watching preferentially enhancing coupling in sensory and language systems. Regions with more stable functional connectivity across states showed stronger coupling. Older age was associated with lower auditory and somatomotor coupling in both cohorts, alongside heterogeneous increases in association cortex. Together, we show that cognitive context shapes structure-function alignment, supporting a framework of complementary structure-constrained and distributed-integrative modes of communication.

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Pedersen, R., Sala-Llonch, R., Persson, J., Salami, A.. 2026-11-13. State-dependent structure-function coupling reflects dynamic engagement of the brain's structural scaffold. https://doi.org/10.64898/2026.11.12.766152

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